Action of lnhibitor in Serum of Patients with Myasthenia Gravis on Acetylcholine Synthesis

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It is generally considered that the disease process in myasthenia gravis involves a defect at the neuromuscular junction, but the entity remains obscure. Possible mechanisms of the defect in neuromuscular transmission are 1) inhibition of presynaptic acetylcholine (Ach) synthesis, 2) increased hydrolysis of released Ach, and 3) decreased sensitivity of Ach receptor. Many workers reported that prejunctional and postjunctional defects might be caused by a substance present in blood of patients with myasthenia gravis. We found that serum of myasthenic patients inhibits the Ach synthesis, and studied on some properties of theinhibitor.<BR>Inhibition of the Ach synthesis by addition of either serum of normal persons or myasthenic patients were examined by using both slices and homogenate of rat brain cortex. Assays of Ach formed were carried out on the rectus abdominis muscle of a frog.<BR>Inhibition of the Ach synthesis increases approximately in parallel with concentration of serum in the reaction mixture, which means the presence of an inhibitory substance in serum of the patients. The supernatant of boiled serum of the patients (boiled sup of serum) inhibits the Ach synthesis to the same extent as untreated serum. While the inhibitory effect decreases when the boiled sup of serum is treated with acid (pH 2.0), it almost disappears when treated with alkali (pH 10.0). The inhibitor is not extracted by chloroform-methanol (2: 1) and the inhibition by the boiled sup is not affected by this treatment.<BR>The serum of the patients was fractionated to three parts by means of Sephadex G-50 column; I: fraction including protein, II: intermediate fraction, III: fraction including salts. Fraction I shows the inhibition of 17.5%, and fraction II that of 7.1%, but fraction III no inhibition. In case of the boiled sup of serum, however, the inhibitionis observed only in fraction II by 12.5%. It is postulated that the inhibitor in the patients' serum has the nature to bind with protein and has particularly labile structures againstalkali, and that the substance may be amine or peptide.<BR>When the Ach synthesis is carried out by the method of Gardiner with a water-treated and ultracentrifuged (105,000×g, 60min) preparation of rat brain cortex inthe reaction mixture containing acetyl-CoA, the patients' serum has also an inhibitory effect of 20-27%. This result suggests that the inhibition of the Ach synthesis is closely related to cholineacetylase rather than membrane transport, and the inhibitor of the Ach synthesis in rat brain cortex may have the same activity at the neuromuscular junction, too.
Japan Society of Clinical Chemistryの論文

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中尾量保
大阪大学医学部曲直部外科

Action of lnhibitor in Serum of Patients with Myasthenia Gravis on Acetylcholine Synthesis

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